tbuckley/cabot-search huggingface dataset:
Abstract 12445: Association of Remnant Cholesterol With Incident Cardiovascular Disease Among Koreans: A National Population-Based Study
Authors: Sang Jun Lee, Se-Eun Kim, Tae-Hwa Go, Dae Ryong Kang, Young-In Kim, Ho-Seong Jeon, Dong-Hyuk Cho, Jangyoung Kim, Sang Hyun Kim, Sung Gyun Ahn
Journal: Circulation (2022)

Aims: We sought to investigate the association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident atherosclerotic cardiovascular disease (ASCVD) in various subgroups among Koreans. Methods: National Health Information Database, collated by Korean National Health Insurance System, was used for analysis. Among the individuals between 40 and 70 years of age and without history of cerebro-cardiovascular disease, those who had twice or more health screenings between 2009 and 2011 were selected. All subjects were divided into 4 groups by LDL-C level of 3.4 mmol/L (130mg/dL) and remnant-C level of 0.8mmol/L (30mg/dL). The primary outcome was defined as the incidence of ASCVD. Results: 3,686,034 individuals (45.6% women) fulfilled the study requirements. By the end of 2017, 144,004 ASCVD events occurred. High remnant-C and low LDL-C group was 19% of total. Compared with low remnant-C and low LDL-C group, the high remnant-C and high LDL-C group had highest ASCVD risk (HR 1.266, CI 1.243-1.289) and the high remnant-C alone group (HR 1.102, CI 1.087-1.118) had similar ASCVD risk to the high LDL-C alone group (HR 1.098, CI 1.083-1.113). The association of high remnant-C (≥0.8 mmol/L) with an increased ASCVD risk was consistent across various strata. Remnant-C levels remained significantly to associate with ASCVD after adjustment for several confounders, including LDL-C levels. Conclusions: Elevated remnant-C values, apart from LDL-C levels, were independently associated with a risk of incident ASCVD. Combination of high LDL-C and high remnant-C levels better predicted ASCVD incidence than each one alone. Therefore, we might take into account remnant-C measurement in risk stratification for primary prevention of ASCVD.
Abstract 12372: In-Situ Constructive Myocardial Regeneration With A 3-D Tissue-Engineered Cardiac Patch Combined Myocardial Cells and Extracellular Matrix
Authors: Tatsuya Watanabe, Yojiro Koda, Keigo Kawaji, Austeja Staneviciute, Andrew Beaser, Marcella K Vaicik, Takeyoshi Ota
Journal: Circulation (2022)

Objective: We developed a tissue-engineered cardiac patch derived from a myocardial cell block reinforced with extracellular matrix (ECM) to enhance in-situ myocardial regeneration. We sought to assess constructive and functional regeneration of the patch in a porcine preparation. Methods: A scaffold-free myocardial cell block was created with cardiomyocytes and embryonic fibroblast cells using a 3D Net Mold system( Fig.A ). The myocardial cell block incorporated with ECM sheets(cbECM) was surgically implanted into a right ventricular (RV) of a healthy porcine model (n=4), or Dacron patches (n=4) which served as control ( Fig.B,C ). After 60 days, the implanted patches were assessed with cardiac magnetic resonance imaging including the rest perfusion(RP) analysis, Extracellular volume fraction(ECV) analysis, and electroanatomical mapping(EAM) studies as well as post euthanasia analyses including histological analysis and Quantitative reverse transcription-polymerase chain reaction(RT-PCR). Results: RP analysis showed improved regional tissue perfusion in the cbECM patch area( Fig.D ). ECV values were much less in the cbECM patch compared to Dacron patch(36.1±3.6 vs. 72.0±13.6, p=0.012)( Fig.E ), which implied the cbECM patch had less fibrosis and edema. EAM revealed regenerated electrical conductivity in the patch as evidenced by relatively preserved voltage regions (1.11±0.8 mV) compared with the normal RV control 4.7±2.8 mV( Fig.F ). RT-PCR showed increased expression of growth factors in cbECM group( Fig.G ). Repopulation of site-specific host cells including premature cardiomyocyte and active vasculogenesis were confirmed with histology/tissue analysis( Fig.H ). Conclusions: The tissue-engineered cardiac patch facilitated in-situ constructive functional myocardial regeneration with increased regional tissue perfusion, and positive electrical activity in the porcine RV model.
Abstract 12486: Impact of New-Onset Persistent Left Bundle Branch Block on Reverse Cardiac Remodeling and Clinical Outcomes After Transcatheter Aortic Valve Replacement
Authors: Kyu Kim, Young-Guk Ko, Chi Y Shim, JiWung Ryu, Yong-Joon Lee, Jiwon Seo, Seung-Jun Lee, Iksung Cho, Sung-jin Hong, Byeong-Keuk Kim, Geu-Ru Hong, Jong-Won Ha, Donghoon Choi, Myeong-Ki Hong
Journal: Circulation (2022)

Background: The clinical implication of new-onset left bundle branch block (LBBB) after transcatheter aortic valve replacement (TAVR) remains controversial. We investigated the impact of new-onset persistent LBBB on reverse cardiac remodeling and clinical outcomes after TAVR. Methods: Among 478 patients who had undergone TAVR for symptomatic severe aortic stenosis from 2011 to 2021, we analyzed 364 patients after excluding patients with pre-existing intraventricular conduction disturbance or a pacing rhythm before or during the indexed hospitalization for TAVR. Echocardiographic variables of cardiac remodeling at baseline and 1 year after TAVR were comprehensively analyzed. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure. Secondary outcomes were all-cause death and individual components of the primary outcome. Result: New-onset persistent LBBB occurred in 41 (11.3%) patients after TAVR. The no LBBB group showed a significant increase in the left ventricular (LV) ejection fraction and decreases in LV dimensions, the left atrial volume index, and LV mass index 1 year after TAVR (all p&lt;0.001). However, the new LBBB group showed no significant changes in these parameters. During a median follow-up of 18.1 months, the new LBBB group experienced a higher incidence of primary outcomes (hazard ratio [HR]: 5.03; 95% confidence interval [CI]: 2.60-9.73; p &lt; 0.001) and all-cause death (HR: 2.80; 95% CI: 1.38-5.69; p = 0.003). The data were similar after multivariable regression analysis. Conclusion: New-onset persistent LBBB after TAVR is associated with insufficient reverse cardiac remodeling and increased adverse clinical events.
Abstract 12278: Relationship Between Amiodarone Response Prior to Ablation and One Year Outcomes of Catheter Ablation for Atrial Fibrillation
Authors: Ritu Yadav
Journal: Circulation (2022)

Introduction: Catheter ablation for atrial fibrillation is a common therapeutic strategy for paroxysmal and persistent AF patients, but long-term success rates are imperfect. Maintenance of sinus rhythm prior to ablation with antiarrhythmic drug therapy has improved outcomes in patients undergoing ablation compared to ablation procedure alone. Amiodarone has superior efficacy relative to other AADs. Whether the failure of amiodarone to maintain sinus rhythm prior to ablation is a predictor of poor outcomes is unknown. Methods: Total 307 patients received amiodarone in a span of 1y before undergoing catheter ablation for AF from January 2014 to March 2019. Patients were divided into amiodarone success (n=183) and amiodarone failure (n=124) groups based on the response to pre-ablation amiodarone treatment. Follow-up was done for 12 months post-ablation to assess outcomes (arrhythmia recurrence and adverse events). Procedural success was defined by the absence of documented arrhythmia (&gt;30s) without any antiarrhythmic agents beyond a 90d blanking period. Results: Ablation procedure success rate at 1y was 57.7% overall. 1y success rate in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs. 60.5%; p=0.54). Success rates following ablation did not vary by the response to amiodarone when analyzed for paroxysmal or persistent AF subgroups. Conclusion: Failure to restore and maintain sinus rhythm on amiodarone therapy is not a predictor of adverse ablation procedure outcomes and should not be used as a patient selection criteria for consideration of ablation.
Abstract 11621: Risk Factors for Cardiovascular (CV) Outcomes in Patients With Essential Thrombocythemia: An Analysis of the National Inpatient Sample (NIS)
Authors: Guillermo Tafur, Hardy Sandefur, Marisa Durante, Lolita Golemi, Pranav Kandula, Alfonso J Tafur
Journal: Circulation (2022)

Introduction: Essential Thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an overproduction of platelets in the bone marrow. Patients suffering from this condition are at a higher risk for CV complications. Studies have demonstrated a prothrombotic state in ET patients and a significant mortality rate stemming from thrombotic complications. However, data regarding the risk of hospitalization for CV events in patients with ET are scarce. Therefore, our objective was to identify risk factors for CV outcomes among patients with ET. Methods: We performed a retrospective analysis of the National Inpatient Sample (NIS) from 2016 to 2017. Patients included were at least 18 years of age and had an ICD-10 diagnosis of ET. To identify CV outcomes, an ICD-10 code for VTE, Stroke, ACS, or a Major Adverse Limb Event had to be present in the top three discharge diagnoses. We identified common chronic comorbidities and performed binary logistic regression to identify risk factors for hospitalizations due to CV outcomes. Those factors were then validated with the 2018 and 2019 NIS databases. Results: We identified a total of 234,225 (weighted) NIS patients with ET. The mean age was 59.72 years (SD = 18.679), and patients were predominantly female (57%). CV outcomes were present in 18,955 cases (8.10%). Significant predictors for CV outcomes among patients with ET included valvular disease (VHD) (odds ratio, 1.33 [95% CI, 1.23-1.43]; P&lt;0.0001), peripheral vascular disease (PVD) (odds ratio, 1.97 [95% CI, 1.87-2.07]; P&lt;0.0001), paralysis (odds ratio, 1.63 [95% CI, 1.54-1.73]; P&lt;0.0001), and hypertension (HTN) (odds ratio, 1.36 [95% CI, 1.32-1.41]; P&lt;0.0001). Upon re-testing with 237,345 (weighted) ET patients from the 2018 and 2019 NIS cohorts, significant risk factors included VHD (odds ratio, 1.99 [95% CI, 1.90-2.08]; P&lt;0.001), PVD (odds ratio, 2.07 [95% CI, 1.98-2.16]; P&lt;0.001), paralysis (odds ratio, 3.35 [95% CI, 3.21-3.49]; P&lt;0.0001), and HTN (odds ratio, 1.68 [95% CI, 1.62-1.74]; P&lt;0.001). Conclusion: Among patients with ET in the 2016-2019 NIS cohorts, VHD, PVD, HTN, and paralysis were associated with the greatest risk of CV outcomes. Patients hospitalized with ET may benefit from increased risk management in the setting of these comorbidities.
Abstract 12273: Crispr-Mutation of the Na <sup>+</sup> -k <sup>+</sup> Pump β1-Subunit Protects Against Cardiac Fibrosis and Heart Failure in Mice
Authors: Di Wu, Elijah Genetzakis, Hooi H Ng, Giannie Barsha, Marie Besnier, Kristen Bubb, Gemma A Figtree
Journal: Circulation (2022)

Introduction: The Na+-K+ pump controls translocation of Na+ and K+ across the cell membrane which indirectly affects heart muscle contraction. Glutathionylation of the Na+-K+ pump’s β1 subunit (NKβ1) is a reversible post-translational oxidative modification, where a glutathione adduct forms a disulphide bond with the cysteine residue at site 45, leading to a reduction in pump activity. Using CRISPR/Cas9 technology, we created a transgenic mouse line (CRISPR-β1) that has a mutation in cysteine to serine at site 45 on NKβ1, causing insensitivity to β1-GSS. Hypothesis: We hypothesize that a mutation of the β1-GSS can inhibit transverse aortic constriction (TAC)-induced cardiac fibrosis. Methods and Results: TAC was induced in both the wild-type (WT) and CRISPR-NKβ1 mutated mice (CRISPR-β1) over a period of four weeks. Gene sequencing showed that cysteine 45 was replaced by serine, and immunoprecipitation of the free cysteine demonstrated that cysteine 45 was mutated in the β1 subunit of the CRISPR-β1 mice hearts. TAC significantly reduced cardiac function in the WT but not the CRISPR-β1 mice (ejection fraction: WT TAC: 36.24% ± 3.49%; CRISPR-β1 TAC: 57.5% ± 3.41%). Similarly, we found that the CRISPR-β1 mice were protected from cardiac hypertrophy, as evidenced by a significant reduction in cardiomyocytes size (WT TAC: 452.1 μm2 ± 30.74 μm2 ; CRISPR-β1 TAC: 271.1 μm 2 ± 11.0 μm 2 ). TAC significantly increased interstitial and perivascular fibrosis in the left ventricles of WT but not the CRISPR-β1 mice (interstitial: WT TAC: 18.4% ± 1.96%; CRISPR-β1 TAC: 5.2% ± 1.62%, perivascular: WT TAC: 42.6% ± 4.5%; CRISPR-β1 TAC: 22.01% ± 1.6%). Cardioprotective effects observed in the CRISPR-β1 mice were at least in part attributed to a significant reduction in the expression of ANP, BNP, Tgfb1, Fn1 and Ctgf genes. Conclusions: Our data indicate that CRISPR mutation of the Na+-K+ pump’s β1 subunit prevents the development of cardiac fibrosis and heart failure in a TAC-induced mouse model.
Abstract 11848: Female Gender, Lower Household Income, Non-Medicare Beneficiaries, and Being a Resident of Small-Sized Population Areas are Associated With In-Hospital Mortality Among Patients Living With Human Immunodeficiency Virus (plwh) With Cardiac Arrest: A Retrospective Analysis of National Inpatient Sample Database From 2016 to 2019
Authors: Saeed Shoar, Khaled Ali, ahmad abdelrazek, Sadegh Asadi
Journal: Circulation (2022)

Background: Despite major scientific advances in contemporary resuscitation, survival outcome in both in-hospital and out-of-hospital cardiac arrest (CA) patients remain dismal. Objective: How do individuals’ demographic and socioeconomic status, insurance status, and hospital characteristics play a role in survival following CA in patients living with human immunodeficiency virus (PLWH)? Methods: Using the ICD10 codes B20-B24 for HIV and ICD10 code I46 for CA, we queried the national inpatient sample from 2016 to 2019 to identify admission cases of PLWH with CA. Weighted data was analyzed using logistic regression model. Results: Out of 475,910 admissions for PLWH from 2016 to 2019, 4,650 cases had CA. Of these, 3,065 patients died during the course of hospitalization (65.9%). Although mortality rate decreased for both genders over time, the decline was steeper for females (72% in 2016 to 62% in 2019) compared to the males (68% in 2016 to 64% in 2019). Female gender was however associated with an increased odds of death compared to male (OR: 1.2, 95%CI: 1-1.3, p=0.03). Asian or Pacific Islanders were associated with a lower odds ratio for mortality (OR: 0.6, 95%CI: 0.3-1, p=0.04). Additionally, beneficiaries of all the insurance types had higher odds of mortality compared to Medicare beneficiaries (OR between 1.8 and 3). The odds of death decreased with increasing household income (OR between 0.7 and 0.9). Patients admitted to the hospitals of West South Central (OR:1.6) and Pacific Regions (OR:1.7) had a higher mortality rate as had those residing in areas with less than 250,000 populaces (OR: 1.7). Conclusion: Despite declining trend in mortality from CA among hospitalized PLWH, more than 60% of the cases die during their hospital stay. Female gender, lower household income, non-Medicare beneficiaries, and being a resident of smaller size population areas were associated with higher mortality among PLWH hospitalized with CA.
Abstract 12601: Oral Xe-Cyclodextrin Provides Neuroprotection for Ischemic Stroke Treatment
Authors: Xing Yin, Brion Frierson, Jean G Wu, Melanie R Moody, Wei Guo, Jonathan Claypool, Sean I Savitz, Jaroslaw A Aronowski, David D McPherson, keith booher, Shaoling Huang
Journal: Circulation (2022)

Introduction: Ischemic stroke is one of the main causes of long-term morbidity/mortality and early treatment is key. Xenon (Xe) has demonstrated powerful neuroprotective effects on both ischemic and hemorrhagic stroke, but its clinical and long-term outpatient administration is limited by currently available delivery methods. Development of an oral Xe formulation is an attractive strategy for stroke treatment in the field. We developed a Xenon (Xe)-cyclodextrin (CD) oral formulation. Hypothesis: Xe-CD formulation can be delivered orally for acute stroke treatment. Methods: A stable, oral Xe-CD clathrate (Xe solid gas) was formed by pressurizing Xe (3 atm) into 14% alpha-cyclodextrin at room temperature. Xe concentration was measured by GC-MS. Rat middle cerebral artery occlusion (MCAO) was induced by intraluminar suture. The animals were divided into groups: stroke (n=4); stroke with CD (n=3); stroke with 0.5 ml Xe-CD (n=3); stroke with 1.0 ml Xe-CD (n=3); and stroke with 1.5 ml Xe-CD (n=3). Treatments were administered by gavage once a day for 3 days. At day 3, neurological behavior testing was conducted. The infarct size and neuronal death were assessed and normalized by total brain volume. Results: There are 1.56 mM Xe clathrate per 0.6 mM alpha-cyclodextrin. MCAO for 2 hours induced 21% ± 3.6% infarct volume. Xe-CD treatment dose-dependently reduced the infarct size to 18.9% ± 2.3% by 0.5 ml Xe-CD, 6.7% ± 1.8% by 1.0 ml Xe-CD, and 4.8% ± 1.2% by 1.5 ml Xe-CD (Fig. 1A). Behavioral test assessment using forelimb placement rate and Rotarod score matched infarct size. TUNEL staining demonstrated significant decreases in apoptosis in stroke rats treated with 1.5 ml Xe-CD (Fig. 1B). Conclusions: We have demonstrated oral Xe-CD formulation ameliorates neuronal apoptosis and reduces infarct size. Xe-CD represents a promising therapeutic for ischemic stroke treatment.
Abstract 12110: The Multi-Racial Clinical and Familial Characteristics of Early and Late Onset Atrial Flutter
Authors: Ana S Ongtengco, Victor Qiao, Hatem Hassaballa, Malek Allababidi, Shaurya Dhingra, Atreya Mishra, Ashwini Deshpande, Yining Chen, Bahaa Al-azzam, Sreenivas Konda, David Tofovic, Dawood Darbar
Journal: Circulation (2022)

Introduction: Studies in Whites of European descent have shown that atrial fibrillation (AF) have a strong genetic component especially in probands with early-onset (EO) AF. However, the role of family history in the pathogenesis of EO atrial flutter (EOAFL) across race-ethnicity remains unclear. Here, we sought to determine if African American, European American, and Hispanic/Latino probands with EOAFL have a higher rate of arrhythmia recurrence in first-degree family members than ethnically-matched patients with late-onset AFL (LOAFL). Methods: In this cohort study, 917 adults with AFL were identified between 2015 and 2021 across 3 sites in the Chicagoland area. EOAFL was defined as AFL occurring before 60 years of age. Primary analysis of reported family history in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram was done. Results: Those with EOAFL were more overweight, Black or White, and had more comorbidities ( Table 1 ). Multivariate analysis showed that BMI ≥ 40 kg/m 2 (odds ratio [OR]: 5.4; 95% confidence interval [CI]: 3.2-9.4, p &lt;0.001) and a family history (OR: 3.7; 95% CI: 2.1-6.9, P &lt;0.001) carried the highest adjusted odds of EOAFL followed by alcohol use (OR: 2.1; 95% CI: 1.5-3.0, P &lt;0.001), Black race (OR: 1.6; 95% CI: 1.1-2.3, P =0.021), and heart failure (OR: 1.4; 95% CI: 1-1.9, P =0.03). Adjusting for effect modification on the association of family history and race, among Whites, the odds of EOAFL in patients with family history was 6.1 (95% CI: 2.1-22.3, P =0.002) comparative to those with no family history, and among Blacks, it was 4.9 (95% CI: 1.6-6.1, P =0.021). Conclusion: Obesity and family history were strongly associated with EOAFL. Whites with EOAFL were more likely to have a first-degree relative with AF/AFL when compared to Blacks or Hispanics/Latinos. These findings support genetic predisposition to EOAFL across all 3 races.
Abstract 11910: Contemporary In-Hospital Outcomes of Bifurcation Percutaneous Coronary Interventions: Update From the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION)
Authors: Bahadir Simsek, Spyridon Kostantinis, Judit Karacsonyi, Evangelia Vemmou, Ilias Nikolakopoulos, maen assali, M Nicholas Burke, Santiago Garcia, Yale Wang, Mario Goessl, Jay Traverse, Anil Poulose, Ivan Chavez, Paul Sorajja, Michael R Mooney, Olga Mastrodemos, Bavana V Rangan, Emmanouil S Brilakis
Journal: Circulation (2022)

Introduction: Bifurcation percutaneous coronary intervention (PCI) techniques are rapidly evolving and can be challenging to perform. Methods: We examined the angiographic, procedural characteristics, and outcomes of 472 bifurcation PCIs in Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION, NCT05100992). Results: A total of 472 bifurcation PCIs were included. Mean age was 67±12 years, 74% were men with a high prevalence of comorbidities: hypertension (81%), diabetes mellitus (36%), dyslipidemia (90%). Overall technical success was 95%. The incidence of in-hospital major adverse cardiovascular events (MACE) was 5.1%. The most common stenting strategy was provisional (71%), double-kissing (DK) crush (12%), mini-crush wish 2 stents (3%), culotte (3%), T-and protrusion (4%), and T-stenting (1.5%). Patients treated with the DK-crush had more severe stenosis of the left main (35%±38 vs. 19%±30, p&lt;0.001), proximal left anterior descending (68%±29, vs. 52%±35, p=0.001), and side branch lesion (82%±15, 51%±36, p&lt;0.001). Medina classification was more often 1,1,1 (79% vs. 39%, p&lt;0.001), with higher use of intravascular ultrasound/optical coherence tomography (57% vs. 31%, p&lt;0.001) compared to non-DK crush. The DK-crush required use of more contrast and took longer to perform (Table). Conclusions: Despite high patient comorbidity, bifurcation PCI can be performed with high technical success and low in-hospital MACE rates. DK-crush technique was more commonly preferred in bifurcation lesions with more severe/proximal vessel involvement.
Abstract 11482: The PCSK9-Targeted Antisense Oligonucleotide AZD8233 Reduces LDL-C, ApoB, and Lp(a) in Patients With Dyslipidemia on Statin Treatment - Data From the Phase 2b ETESIAN Study
Authors: Alexis Hofherr, Jennifer Schumi, Anna Rudvik, Rick Vega, Tina Ryden-Bergsten, Eva Hurt-Camejo, Per Johanson, Bjorn C Carlsson
Journal: Circulation (2022)

Introduction: Elevated blood levels of lipoprotein(a) [Lp(a)] are an independent causal risk factor for atherosclerotic cardiovascular disease. Lp(a) particles are formed by a lipid domain and an apolipoprotein B (apoB) protein that is bound to apolipoprotein(a). Standard low-density lipoprotein cholesterol (LDL-C) and ApoB lowering treatments have minimal Lp(a)-lowering efficacy. We have previously shown that AZD8233 inhibits hepatic PCSK9 synthesis and causes substantial reductions in LDL-C. Here we report the significant effects of AZD8233 on Lp(a) and ApoB. Methods: ETESIAN was a multicenter phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study (NCT04641299). Eligible participants were 18-75 years old, on statin therapy, with LDL-C of ≥ 70 to &lt; 190 mg/dL, and with fasting triglycerides of &lt; 400 mg/dL. Participants were randomized 1:1:1:1 to subcutaneous injections (days 1, 8, 29, and 57) of either 15, 50, or 90 mg AZD8233, or placebo. The primary objective was to evaluate the effect of AZD8233 versus placebo on LDL-C at week 12. Secondary objectives were to assess Lp(a) levels and other lipid parameters. Results: A total of 119 patients were enrolled in ETESIAN. AZD8233 was well tolerated and demonstrated dose-dependent and clinically meaningful reductions in LDL-C, Lp(a), and ApoB ( Table ). The relative distribution of these effects across participant subgroups and the interaction of effects on Lp(a), ApoB, and LDL-C will be presented. Conclusion: In patients with dyslipidemia on statins, AZD8233 caused substantial reductions in LDL-C and Lp(a), two independent risk factors for major adverse cardiovascular events. The broad lipid-modifying effect of AZD8233 may, hence, provide an opportunity to reduce cardiovascular risk in patients with ASCVD beyond currently available medications.